The aims of this research are to identify further the feedback loops that regulate hemopoiesis by exploitation of cell lines that have been isolated and carried in culture. The H-1 cell line produces GM-CSF, a labile inhibitor of granulopoiesis and probably an inhibitor of BFU-E proliferation. Further studies have shown the existence of the BFU-E inhibition to be equivocal. The H-1 cell was derived from bone marrow cells in liquid Dexter culture and has the characteristics of an adventitial reticular cell. The MAC line produces CSF and in vivo induces a granulocytosis, whereas H-1 line does not induce granulocytosis. We will investigate why the H-1 line does not induce granulocytosis. We further will investigate why the H-1 line does not produce a granulocytosis in vivo and the MAC line does, although both produce GM-CSF. We now have two sublines of MAC, both of which are avid producers of CSR, but only one line produces a granulocytosis upon transplantation. Earlier studies showed that an osteosarcoma increases CFU-S content of bone marrow. We will induce more osteosarcoma by 55FE and test for a pluricellpoietin and, if present, commence its isolation and characterization. Through the above and allied in vivo and in vitro studies, we will define feedback loops regulating hemopoiesis, an understanding of which is essential for pathogenesis of diseases of hemopoiesis and their control. (M)